One of the most enigmatic features of the complex disease multiple sclerosis (MS) is the observation that season of birth influences the risk of developing the disease later in life being higher in spring born and lower in fall born individuals. Although the molecular mechanism responsible for this observation is still unknown, several lines of evidence support a role for gestational vitamin D levels in determining this effect. We investigated the association between MS risk, UV light exposure and serum vitamin D levels during gestation in two cohorts of UK born MS patients. The birth distributions of 11,282 Scottish and 8,702 MS English patients were compared to that of the general population. Correlation between risk of MS and average monthly UV light radiation and vitamin D levels in different time windows during gestation in the UK was assessed. The distributions of MS births significantly differed from that of the general population in Scotland (Walter-Elwood test: p = 0.0003) with peaks in April (OR=1.09, 95% CI=1.02–1.16, p=0.007) and May (OR=1.07, 95% CI=1.004-1.14, p=0.036) and trough in September (OR=0.92, 95% CI=0.86-0.99, p=0.025). This was in comparison to previously published data from England/Wales where more MS patients were born in May (and less in November and December). The risk of MS inversely correlated with UV exposure during the second trimester of pregnancy in both Scotland (Spearman correlation coefficient=-0.706, p=0.01) and England/Wales (Spearman correlation coefficient=-0.797, p=0.002). Low vitamin D levels between the 5th and 8th months (in England/Wales) (Spearman correlation coefficient=-0.888, p<0.001) and during the third trimester (in Scotland) (Spearman correlation coefficient=-0.643, p=0.024) were also associated with MS risk. Second trimester UV light radiation and third trimester vitamin D levels inversely correlate with risk of MS in the UK. Gestational vitamin D levels are implicated in the aetiology of MS.

Study Supported By: Multiple Sclerosis Society of Canada; Multiple Sclerosis Society of Italy Disclosure: Dr. Disanto has nothing to disclose. Dr. Ramagopalan has nothing to disclose. Dr. Morahan has nothing to disclose. Dr. Hypponen has nothing to disclose. Dr. Ebers has received personal compensation for activities with Bayer HealthCare Pharmaceuticals. Dr. Ebers has received compensation and/or their research work has been funded, entirely or in part, by a grant to their university. The grant agreement requires that the name of the funding entity and the purpose of the grant may not be disclosed. The funding entity is a nonprofit tax-exempt organization. Dr. Chaplin has nothing to disclose.